WO2016102716A1 - Nouveaux anticorps anti-adam17 humanisés - Google Patents
Nouveaux anticorps anti-adam17 humanisés Download PDFInfo
- Publication number
- WO2016102716A1 WO2016102716A1 PCT/EP2016/050029 EP2016050029W WO2016102716A1 WO 2016102716 A1 WO2016102716 A1 WO 2016102716A1 EP 2016050029 W EP2016050029 W EP 2016050029W WO 2016102716 A1 WO2016102716 A1 WO 2016102716A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- humanized antibody
- binding fragment
- antigen binding
- seq
- cancer
- Prior art date
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/2896—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants against molecules with a "CD"-designation, not provided for elsewhere
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/18—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans
- C07K16/28—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants
- C07K16/30—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against material from animals or humans against receptors, cell surface antigens or cell surface determinants from tumour cells
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K16/00—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies
- C07K16/40—Immunoglobulins [IGs], e.g. monoclonal or polyclonal antibodies against enzymes
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/505—Medicinal preparations containing antigens or antibodies comprising antibodies
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/54—Medicinal preparations containing antigens or antibodies characterised by the route of administration
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K39/00—Medicinal preparations containing antigens or antibodies
- A61K2039/545—Medicinal preparations containing antigens or antibodies characterised by the dose, timing or administration schedule
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/20—Immunoglobulins specific features characterized by taxonomic origin
- C07K2317/24—Immunoglobulins specific features characterized by taxonomic origin containing regions, domains or residues from different species, e.g. chimeric, humanized or veneered
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/30—Immunoglobulins specific features characterized by aspects of specificity or valency
- C07K2317/34—Identification of a linear epitope shorter than 20 amino acid residues or of a conformational epitope defined by amino acid residues
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/54—F(ab')2
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/55—Fab or Fab'
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/565—Complementarity determining region [CDR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/50—Immunoglobulins specific features characterized by immunoglobulin fragments
- C07K2317/56—Immunoglobulins specific features characterized by immunoglobulin fragments variable (Fv) region, i.e. VH and/or VL
- C07K2317/567—Framework region [FR]
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/60—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments
- C07K2317/62—Immunoglobulins specific features characterized by non-natural combinations of immunoglobulin fragments comprising only variable region components
- C07K2317/622—Single chain antibody (scFv)
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/73—Inducing cell death, e.g. apoptosis, necrosis or inhibition of cell proliferation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/70—Immunoglobulins specific features characterized by effect upon binding to a cell or to an antigen
- C07K2317/76—Antagonist effect on antigen, e.g. neutralization or inhibition of binding
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07K—PEPTIDES
- C07K2317/00—Immunoglobulins specific features
- C07K2317/90—Immunoglobulins specific features characterized by (pharmaco)kinetic aspects or by stability of the immunoglobulin
- C07K2317/92—Affinity (KD), association rate (Ka), dissociation rate (Kd) or EC50 value
Definitions
- a germline represents the basic genetic message as is transmitted from parent to sibling prior to any functional rearangement in the coding sequence of said gene.
- V variable
- D diversity
- J joining genes
- Germline sequences for human V, D and J genes can be obtained and interrogated from curated databases such as IMGT, UNSWIg, NCBI and VBASE2.
- sequences SEQ ID No. 7 and 8 are corresponding to consensus sequences wherein the potential back-mutations according to the invention are identified.
- the antibody according to the invention may comprise none or at least one back mutation(s).
- Another particular embodiment of the invention is a humanized antibody, or an antigen binding fragment thereof, characterized in that the light chain variable domain consists of the sequence SEQ ID No. 10, or any sequence exhibiting at least 80% identity with SEQ ID No. 10.
- the humanized antibody comprising the light chain variable domain consisting of the sequence SEQ ID No. 10 above mentioned also comprises a heavy chain variable domain having the CDR-L1, CDR-L2 and CDR-L3 of sequences SEQ ID Nos. 1, 2 and 3, respectively.
- the humanized antibody of the invention is characterized in that it inhibits with at least an IC 50 of 500 pM or less, preferentially 200 pM or less, the cellular shedding of at least one substrate of ADAM 17 selected from TNF-a, TGF-a, AREG and HB-EGF.
- the humanized antibody is characterized in that it binds to an ADAM17 epitope with a Kd of about 10 nM or less, preferentially of about 5 nM or less, and more preferentially of about 2 nM or less, as determined by surface plasmon resonance (SPR).
- SPR surface plasmon resonance
- said cancer is a cancer chosen among estrogen-related breast cancer, non-small cell lung cancer, colon cancer and/or pancreatic cancer.
- Expressed antibodies were adjusted to pH 7.5 and purified on protein A sepharose columns with elution by pH shift with Glycine, HC1 0.1 M, pH 3, the resulting eluant was adjusted to pH 7.5 by dialysis against Tris-HCl pH 7.5 solution.
- the protein solutions were normalised by total protein quantification using the bicinchoninic acid assay. Equal quantities of protein were separated by SDS-PAGE in non-reducing conditions, and visualised by GelCode Blue Safe Protein Stain (BioRad).
- Four humanised variants were analysed for germline combination IGHV2-5 and IGKV1-33, Vl-4, and thirteen variants with germlmes IGHV4-4 and IGKV1-39, V5-V17 and hzl022C3.
- hzl022C3 showed a significantly increased inhibition of the release of AREG-Nluc, TGFa-Nluc or HB-EGF-Nluc than ml022C3 (+6.35% ⁇ 1.47%; +6.12% ⁇ 1.13% and +10.15% ⁇ 2.99%) respectively) (figures 2A-2C respectively).
- ADAM 17 expression levels were determined by staining, lxl 0 5 cells/ 100 ⁇ in FACS buffer (PBS containing 1% BSA and 0.01% sodium azide) incubated for 20 min. at 4°C with increasing concentrations of the MAB9301 (Clone 1 1 1633, R&D systems) in order to determine a saturating concentration. Cells were then washed three times in FACS buffer. Cells were resuspended and incubated for 20 min. at 4°C with a goat anti-mouse IgG-Alexa 488 antibody (Invitrogen Corporation, Scotland, # A1 1017). Cells were then washed three times in FACS buffer.
- FACS buffer PBS containing 1% BSA and 0.01% sodium azide
- the CaOV3 xenograft model was set up by cell engraftments on SCID mice as described above.
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Organic Chemistry (AREA)
- Immunology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Medicinal Chemistry (AREA)
- General Health & Medical Sciences (AREA)
- Biochemistry (AREA)
- Proteomics, Peptides & Aminoacids (AREA)
- Molecular Biology (AREA)
- Genetics & Genomics (AREA)
- Biophysics (AREA)
- Cell Biology (AREA)
- Public Health (AREA)
- General Chemical & Material Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Veterinary Medicine (AREA)
- Pharmacology & Pharmacy (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Animal Behavior & Ethology (AREA)
- Peptides Or Proteins (AREA)
- Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
- Preparation Of Compounds By Using Micro-Organisms (AREA)
Abstract
Priority Applications (10)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CN201680007889.3A CN107250162A (zh) | 2014-12-24 | 2016-01-04 | 新的人源化adam17抗体 |
JP2017534270A JP2018502096A (ja) | 2014-12-24 | 2016-01-04 | 新規ヒト化adam17抗体 |
CA2971361A CA2971361A1 (fr) | 2014-12-24 | 2016-01-04 | Nouveaux anticorps anti-adam17 humanises |
EP16700011.6A EP3237008A1 (fr) | 2014-12-24 | 2016-01-04 | Nouveaux anticorps anti-adam17 humanisés |
BR112017013420A BR112017013420A2 (pt) | 2014-12-24 | 2016-01-04 | anticorpo adam17 humanizado |
RU2017125036A RU2017125036A (ru) | 2014-12-24 | 2016-01-04 | Новое гуманизированное антитело к adam17 |
KR1020177018568A KR20170099927A (ko) | 2014-12-24 | 2016-01-04 | 신규 인간화 adam17 항체 |
AU2016204625A AU2016204625A1 (en) | 2014-12-24 | 2016-01-04 | Novel humanized ADAM17 antibody |
US15/538,331 US20180057601A1 (en) | 2014-12-24 | 2016-01-04 | Novel humanized adam17 antibody |
MX2017008475A MX2017008475A (es) | 2014-12-24 | 2016-01-04 | Novedoso anticuerpo humanizado adam17. |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
EP14307185 | 2014-12-24 | ||
EP14307185.0 | 2014-12-24 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO2016102716A1 true WO2016102716A1 (fr) | 2016-06-30 |
Family
ID=52396391
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/EP2016/050029 WO2016102716A1 (fr) | 2014-12-24 | 2016-01-04 | Nouveaux anticorps anti-adam17 humanisés |
Country Status (11)
Country | Link |
---|---|
US (1) | US20180057601A1 (fr) |
EP (1) | EP3237008A1 (fr) |
JP (1) | JP2018502096A (fr) |
KR (1) | KR20170099927A (fr) |
CN (1) | CN107250162A (fr) |
AU (1) | AU2016204625A1 (fr) |
BR (1) | BR112017013420A2 (fr) |
CA (1) | CA2971361A1 (fr) |
MX (1) | MX2017008475A (fr) |
RU (1) | RU2017125036A (fr) |
WO (1) | WO2016102716A1 (fr) |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020021061A1 (fr) | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Anticorps humanisés anti-pd-1 et leurs utilisations |
Families Citing this family (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE102018124785A1 (de) | 2018-10-08 | 2020-04-09 | Schott Ag | Glas mit vorzugsweise erhöhter speicherbarer Zugspannung, chemisch vorgespannter Glasartikel mit vorzugsweise erhöhter speicherbarer Zugspannung, Verfahren zu dessen Herstellung sowie dessen Verwendung |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012104581A1 (fr) * | 2011-02-01 | 2012-08-09 | Cancer Research Technology Limited | Molécules d'anticorps anti-tace et leurs utilisations |
WO2014157229A1 (fr) * | 2013-03-28 | 2014-10-02 | 国立大学法人東北大学 | Epitope peptidique tace, anticorps protéique anti-tace humain et hybridome produisant des anticorps |
Family Cites Families (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2001036445A1 (fr) * | 1999-11-18 | 2001-05-25 | The Brigham And Women's Hospital, Inc. | Compositions et procedes pour un diagnostic et un traitement ameliores des tumeurs des cellules germinales |
EP1449538A1 (fr) * | 2003-02-21 | 2004-08-25 | Max-Planck-Gesellschaft zur Förderung der Wissenschaften e.V. | Inhibition de TACE ou amphirégulin pour moduler la transactivation de signaux récepteur EGF |
AU2005316217A1 (en) * | 2004-12-17 | 2006-06-22 | Memorial Sloan Kettering Cancer Center | Regulation of metalloprotease cleavage of cell surface proteins |
US9845482B2 (en) * | 2011-06-29 | 2017-12-19 | The General Hospital Corporation | Compositions and methods for enhancing bioenergetic status in female germ cells |
-
2016
- 2016-01-04 WO PCT/EP2016/050029 patent/WO2016102716A1/fr active Application Filing
- 2016-01-04 CN CN201680007889.3A patent/CN107250162A/zh active Pending
- 2016-01-04 MX MX2017008475A patent/MX2017008475A/es unknown
- 2016-01-04 JP JP2017534270A patent/JP2018502096A/ja active Pending
- 2016-01-04 RU RU2017125036A patent/RU2017125036A/ru not_active Application Discontinuation
- 2016-01-04 KR KR1020177018568A patent/KR20170099927A/ko unknown
- 2016-01-04 AU AU2016204625A patent/AU2016204625A1/en not_active Abandoned
- 2016-01-04 EP EP16700011.6A patent/EP3237008A1/fr not_active Withdrawn
- 2016-01-04 BR BR112017013420A patent/BR112017013420A2/pt not_active Application Discontinuation
- 2016-01-04 CA CA2971361A patent/CA2971361A1/fr not_active Abandoned
- 2016-01-04 US US15/538,331 patent/US20180057601A1/en not_active Abandoned
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2012104581A1 (fr) * | 2011-02-01 | 2012-08-09 | Cancer Research Technology Limited | Molécules d'anticorps anti-tace et leurs utilisations |
WO2014157229A1 (fr) * | 2013-03-28 | 2014-10-02 | 国立大学法人東北大学 | Epitope peptidique tace, anticorps protéique anti-tace humain et hybridome produisant des anticorps |
Non-Patent Citations (7)
Title |
---|
"Remington's Pharmaceutical Science", 1985, MACK PUBLISHING COMPANY |
CHEN Y. ET AL., J MOL BIOL., vol. 293, no. 4, 1999, pages 865 - 81 |
LEFRANC M.-P., IMMUNOLOGY TODAY, vol. 18, 1997, pages 509 |
LEFRANC M.-P., THE IMMUNOLOGIST, vol. 7, 1999, pages 132 - 136 |
LEFRANC, M.-P.; POMMIE, C.; RUIZ, M.; GIUDICELLI, V.; FOULQUIER, E.; TRUONG, L.; THOUVENIN-CONTET, V.; LEFRANC, DEV. COMP. IMMUNOL., vol. 27, 2003, pages 55 - 77 |
STEWARD ET AL.: "Solid phase peptides synthesis", 1984, PIERCE CHEM. COMPANY |
TATUSOVA ET AL.: "Blast 2 sequences - a new tool for comparing protein and nucleotide sequences", FEMS MICROBIOL., vol. 174, 1999, pages 247 - 250 |
Cited By (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO2020021061A1 (fr) | 2018-07-26 | 2020-01-30 | Pieris Pharmaceuticals Gmbh | Anticorps humanisés anti-pd-1 et leurs utilisations |
Also Published As
Publication number | Publication date |
---|---|
AU2016204625A1 (en) | 2017-07-13 |
CA2971361A1 (fr) | 2016-06-30 |
MX2017008475A (es) | 2018-02-21 |
EP3237008A1 (fr) | 2017-11-01 |
BR112017013420A2 (pt) | 2018-02-06 |
CN107250162A (zh) | 2017-10-13 |
KR20170099927A (ko) | 2017-09-01 |
US20180057601A1 (en) | 2018-03-01 |
JP2018502096A (ja) | 2018-01-25 |
RU2017125036A (ru) | 2019-01-24 |
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